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Topic Review
Heme Oxygenase-1 and Osteoarthritis
Osteoarthritis (OA) is a common aging-associated disease that clinically manifests as joint pain, mobility limitations, and compromised quality of life. Today, OA treatment is limited to pain management and joint arthroplasty at the later stages of disease progression. OA pathogenesis is predominantly mediated by oxidative damage to joint cartilage extracellular matrix and local cells such as chondrocytes, osteoclasts, osteoblasts, and synovial fibroblasts. Under normal conditions, cells prevent the accumulation of reactive oxygen species (ROS) under oxidatively stressful conditions through their adaptive cytoprotective mechanisms. Heme oxygenase-1 (HO-1) is an iron-dependent cytoprotective enzyme that functions as the inducible form of HO. HO-1 and its metabolites carbon monoxide and biliverdin contribute towards the maintenance of redox homeostasis. HO-1 expression is primarily regulated at the transcriptional level through transcriptional factor nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), specificity protein 1 (Sp1), transcriptional repressor BTB-and-CNC homology 1 (Bach1), and epigenetic regulation. Several studies report that HO-1 expression can be regulated using various antioxidative factors and chemical compounds, suggesting therapeutic implications in OA pathogenesis as well as in the wider context of joint disease. 
  • 557
  • 08 Apr 2021
Topic Review
Seaweeds and Cardiovascular Disease
Cardiovascular disease (CVD), which involves the onset and exacerbation of various conditions including dyslipidemia, activation of the renin–angiotensin system, vascular endothelial cell damage, and oxidative stress, is a leading cause of high mortality rates and accounts for one-third of deaths worldwide. Accordingly, as dietary changes in daily life are thought to greatly reduce the prevalence of CVD, numerous studies have been conducted to examine the potential use of foods and their bioactive components for preventing and treating CVD. In particular, seaweeds contain unique bioactive metabolites that are not found in terrestrial plants because of the harsh environment in which they survive, leading to in vitro and in vivo studies of their prevention and treatment effects. 
  • 556
  • 24 Sep 2021
Topic Review
Endocrine-Disrupting Chemicals and Infectious Diseases
Endocrine-disrupting chemicals (EDCs) are hormonally active compounds in the environment that interfere with the body’s endocrine system and consequently produce adverse health effects. Despite persistent public health concerns, EDCs remain important components of common consumer products, thus representing ubiquitous contaminants to humans. While scientific evidence confirmed their contribution to the severity of Influenza A virus (H1N1) in the animal model, their roles in susceptibility and clinical outcome of the coronavirus disease (COVID-19) cannot be underestimated.
  • 551
  • 28 Apr 2021
Topic Review
Glucagon-like Peptide-1 Receptor Agonists
Type 2 diabetes mellitus (T2DM) is a heterogeneous, chronic, progressive metabolic disease accounting for 90–95% of all diabetes. Glucagon-like peptide-1 (GLP-1) receptor agonists are a new class of antihyperglycemic drugs that enhance appropriate pancreatic β-cell secretion, pancreatic α-cell (glucagon) suppression, decrease liver glucose production, increase satiety through their action on the central nervous system, slow gastric emptying time, and increase insulin action on peripheral tissue. They are effective in the management of type 2 diabetes mellitus and have a favorable effect on weight loss. 
  • 548
  • 08 Apr 2022
Topic Review
Genetic Resistance to COVID-19 Virus Entry
Numerous efforts have been made to comprehend the pathogenic and host variables that contribute to COVID-19 susceptibility and pathogenesis. One of these endeavours is understanding the host genetic factors predisposing an individual to COVID-19. Genome-Wide Association Studies (GWAS) have demonstrated the host predisposition factors in different populations. These factors are involved in the appropriate immune response, their imbalance influences susceptibility or resistance to viral infection.
  • 548
  • 13 Jan 2023
Topic Review
Therapeutic Options for Systemic Sclerosis
Systemic sclerosis (SSc) is a severe auto-immune, rheumatic disease, characterized by excessive fibrosis of the skin and visceral organs. SSc is accompanied by high morbidity and mortality rates, and unfortunately, few disease-modifying therapies are currently available. Inflammation, vasculopathy, and fibrosis are the key hallmarks of SSc pathology. There are current and novel treatment options in diminishing SSc-related fibrosis based on selected clinical trials. 
  • 547
  • 25 Feb 2022
Topic Review
The Svedberg Laboratory
The Svedberg Laboratory (TSL) is a university facility, based in Uppsala, Sweden.The activities at TSL are based around the particle accelerator Gustaf Werner cyclotron. The main activity is proton therapy for the treatment of cancer, based on an agreement between the Oncology clinic at Uppsala University Hospital and Uppsala University.Beamtime not used for proton therapy is devoted to commercial neutron and proton irradiation projects, mainly for Radiation testing.There is also some time for basic (academic) research and in this case the experiments should be associated to Uppsala University or to EC projects. TSL is supported by the European Community and belong to the EC projects ERINDA, SkyFlash and CHANDA.
  • 546
  • 27 Oct 2022
Topic Review
Molecular Dynamics Simulations, Cyclodextrin Complexes
Cyclodextrins (CDs) are highly respected for their ability to form inclusion complexes via host–guest noncovalent interactions and, thus, ensofance other molecular properties. Various molecular modeling methods have found their applications in the analysis of those complexes. However, as showed in this entry, molecular dynamics (MD) simulations could provide the information unobtainable by any other means.
  • 545
  • 24 Sep 2021
Topic Review
NLRP3 Inflammasome in Neuromuscular Diseases
Inflammasomes are molecular platforms that are formed and activated by a host in response to pathogen- and damage-associated molecular patterns as well as cellular injury and stress. Inflammasome activation is benefical to the host as it plays a pivotal role in the clearance of the pathogen and restore tissue homeostasis. However, aberrant activation of the NLRP3 inflammasome by a wide variety of sterile triggers, including misfolded protein aggregates drives pathological sterile inflammation and is associated with several neuromuscular diseases. Assembly of the NLRP3 inflammasome leads to the caspase-1-mediated proteolytic cleavage and secretion of key proinflammatory cytokines, interleukin (IL)-1β and IL-18, and a lytic form of cell death known as pyroptosis. These cytokines further amplify inflammatory responses by activating various signaling cascades, leading to the recruitment of immune cells and overproduction of proinflammatory cytokines and chemokines, resulting in a vicious cycle of chronic inflammation and tissue damage.
  • 544
  • 08 Jul 2021
Topic Review
The Side Effects Reported after COVID-19 Immunization
Studies found that all immunizations were safe, with very few or no Side Effects (SEs); however, the form of SEs was shown to be more persistent in DNA- and mRNA-based vaccines, whereas inactivated viral vaccines were associated with longer-duration SEs. Overall, SEs were shown to be more prevalent in women and youngsters. Certain instances of adverse responses have also been observed, although their pathological relationship with COVID-19 immunization has yet to be determined.
  • 543
  • 14 Apr 2022
Topic Review
Chatbots in Critical Care Nephrology
The exponential growth of artificial intelligence (AI) has allowed for its integration into multiple sectors, including, notably, healthcare. Chatbots have emerged as a pivotal resource for improving patient outcomes and assisting healthcare practitioners through various AI-based technologies. In critical care, kidney-related conditions play a significant role in determining patient outcomes.
  • 543
  • 24 Oct 2023
Topic Review
Dorzagliatin in Type 2 Diabetes Treatment
Achieving glycemic control and sustaining functional pancreatic β-cell activity remains an unmet medical need in the treatment of type 2 diabetes mellitus (T2DM). Glucokinase activators (GKAs) constitute a class of anti-diabetic drugs designed to regulate blood sugar levels and enhance β-cell function in patients with diabetes. A significant progression in GKA development is underway to address the limitations of earlier generations. Dorzagliatin, a dual-acting GKA, targets both the liver and pancreas and has successfully completed two phase III trials, demonstrating favorable results in diabetes treatment. 
  • 543
  • 09 Jan 2024
Topic Review
Diabetes Peptide-Based Drugs
Peptides continue to gain significance in the pharmaceutical arena. Since the unveiling of insulin in 1921, the Food and Drug Administration (FDA) has authorised around 100 peptides for various applications. Peptides, although initially derived from endogenous sources, have evolved beyond their natural origins, exhibiting favourable therapeutic effectiveness. The FDA has authorized a variety of medications for the treatment of diabetes, each designed to target different receptors and operate through diverse mechanisms, depending on the specific type of diabetes being addressed.
  • 543
  • 26 Feb 2024
Topic Review
Yellow Fever Vaccination
Yellow fever (YF) remains a threat to global health, with an increasing number of major outbreaks in the tropical areas of the world over the recent past. In light of this, the Eliminate Yellow Fever Epidemics Strategy was established with the aim of protecting one billion people at risk of YF through vaccination by the year 2026. The current YF vaccine gives excellent protection, but its use is limited by shortages in supply due to the difficulties in producing the vaccine. There are good grounds for believing that alternative fractional dosing regimens can produce strong protection and overcome the problem of supply shortages as less vaccine is required per person. However, immune responses to these vaccination approaches are yet to be fully understood. In addition, published data on immune responses following YF vaccination have mostly quantified neutralising antibody titers. However, vaccine-induced antibodies can confer immunity through other antibody effector functions beyond neutralisation, and an effective vaccine is also likely to induce strong and persistent memory T cell responses.
  • 541
  • 30 Jun 2021
Topic Review
Anti-Angiogenic Therapy
Anti-angiogenics currently used in cancer therapy target angiogenesis by two major mechanisms: (i) neutralizing angiogenic factors or their receptors by using macromolecule anti-angiogenic drugs (e.g., therapeutic antibodies), and (ii) blocking intracellularly the activity of receptor tyrosine kinases with small molecule (Mr < 1 kDa) inhibitors. Anti-angiogenics halt the growth and spread of cancer, and significantly prolong the disease-free survival of the patients. However, resistance to treatment, insufficient efficacy, and toxicity limit the success of this antivascular therapy. Published evidence suggests that four albumin-binding proteins (ABPs) (gp18, gp30, gp60/albondin, and secreted protein acidic and cysteine-rich (SPARC)) could be responsible for the accumulation of small molecule receptor tyrosine kinase inhibitors (RTKIs) in normal organs and tissues and therefore responsible for the side effects and toxicity associated with this type of cancer therapy.
  • 540
  • 20 Apr 2021
Topic Review
Histamine
Histamine [2-(4-imidazolyl)-ethylamine] is a biogenic amine that was first synthesized in the early 1900s. Histamine is a biogenic amine with numerous effects on many cell types, mediated by the activation of its four different histamine receptors (H1–H4Rs).
  • 538
  • 08 Nov 2022
Topic Review
Oncolytic Newcastle Disease Virus
Resistance to therapy is a major obstacle to cancer treatment. It may exist from the beginning, or it may develop during therapy. The review focusses on oncolytic Newcastle disease virus (NDV) as a biological agent with potential to break therapy resistance. This avian virus combines, upon inoculation into non-permissive hosts such as human, 12 described anti-neoplastic effects with 11 described immune stimulatory properties. Fifty years of clinical application of NDV give witness to the high safety profile of this biological agent. In 2015, an important milestone was achieved, namely the successful production of NDV according to Good Manufacturing Practice (GMP). Based on this, IOZK in Cologne, Germany, obtained a GMP certificate for the production of a dendritic cell vaccine loaded with tumor antigens from a lysate of patient-derived tumor cells together with immunological danger signals from NDV for intracutaneous application.
  • 537
  • 09 Jul 2021
Topic Review
Insulin Metabolism in Polycystic Ovary Syndrome
Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in women of reproductive age. Its heterogeneous clinical presentation is characterized by hyperandrogenemia, reproductive changes, polycystic ovary morphology, and insulin resistance (IR). The primary pathophysiological process in its multifactorial etiology has not yet been identified. Although commonly proposed as an initial abnormality, IR is most often looked at in isolation, without the proper investigation of other essential steps in insulin metabolism. 
  • 536
  • 06 May 2023
Topic Review
Hypoglycemia, Vascular Disease and Cognitive Dysfunction in Diabetes
Hypoglycemia has been recognized as a risk factor for diabetic vascular complications and cognitive decline. In this work, gene networks of hypoglycemia and cardiovascular disease, diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, cognitive decline, and Alzheimer’s disease were reconstructed. The gene network of hypoglycemia included 141 genes and 2467 interactions. Hypoglycemia-related genes were overrepresented in the reconstructed gene networks of diabetic complications and comorbidity. Some GO biological processes, including glucose homeostasis, nitric oxide biosynthesis, smooth muscle cell proliferation, ERK1 and ERK2 cascade, were overrepresented in all reconstructed networks.  
  • 536
  • 29 Mar 2022
Topic Review
Photodynamic Therapy and Hyperthermia
Cancer is one of the leading causes of death in humans. Despite the progress in cancer treatment, and an increase in the effectiveness of diagnostic methods, cancer is still highly lethal and very difficult to treat in many cases. Combination therapy, in the context of cancer treatment, seems to be a promising option that may allow minimizing treatment side effects and may have a significant impact on the cure. It may also increase the effectiveness of anti-cancer therapies. Moreover, combination treatment can significantly increase delivery of drugs to cancerous tissues. Photodynamic therapy and hyperthermia seem to be ideal examples that prove the effectiveness of combination therapy. These two kinds of therapy can kill cancer cells through different mechanisms and activate various signaling pathways. Both PDT and hyperthermia play significant roles in the perfusion of a tumor and the network of blood vessels wrapped around it. 
  • 535
  • 08 Oct 2021
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